BEP Study Phase I (Bevacizumab, Everolimus, Panitumumab)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Novartis
Genentech
Amgen
Information provided by (Responsible Party):
Herbert Hurwitz, MD, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT00586443
First received: December 21, 2007
Last updated: April 8, 2014
Last verified: April 2014
  Purpose

Targeting molecular pathways of tumor growth has become a major focus of anti-cancer treatments. This study aims to investigate the toxicity, pharmacokinetics, and preliminary efficacy of the triplet combination of bevacizumab, RAD001, and panitumumab in patients with refractory solid tumors.

This open-labeled, non-randomized phase I trial of bevacizumab, everolimus and panitumumab is designed to assess the safety, tolerability and efficacy of this combination in adult patients with advanced solid tumors.


Condition Intervention Phase
Solid Tumors
Drug: bevacizumab, everolimus, panitumumab
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: A Phase I Study of Bevacizumab, Everolimus, and Panitumumab for Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • To determine the MTD/recommended phase II regimen and evaluate safety of panitumumab added to RAD001 plus bevacizumab in adult patients with advanced solid tumors. [ Time Frame: Every cycle (28-days) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To preliminarily describe any clinical activity (PR, CR or duration of SD) associated with this regimen [ Time Frame: Every cycle (28-days) ] [ Designated as safety issue: No ]

Estimated Enrollment: 44
Study Start Date: November 2007
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
I
This is a Phase I safety study. There is only one arm.
Drug: bevacizumab, everolimus, panitumumab

Cohort # subjects Bevacizumab Everolimus Panitumumab

  • 3 3-6 5 mg/kg IV Q2 weeks 5 mg PO QoD 3.6 mg/kg IV Q2 weeks
  • 2 3-6 5 mg/kg IV Q2 weeks 5 mg PO QoD 4.8 mg/kg IV Q2 weeks
  • 1 3-6 10 mg/kg IV Q2 weeks 5 mg PO QD 4.8 mg/kg IV Q2 weeks

    1. 3-6 10 mg/kg IV Q2 weeks 10 mg PO QD 4.8 mg/kg IV Q2 weeks
    2. 3-6 10 mg/kg IV Q2 weeks 10 mg PO QD 6 mg/kg IV Q2 weeks 3a 10 RPTD* RPTD* RPTD* 3b 10 RPTD** RPTD** RPTD**

      • Panitumumab and RAD001 started on Day 1, bevacizumab started on Day 15. **Bevacizumab and RAD001 started on Day 1, panitumumab started on Day 15.
Other Names:
  • avastin
  • RAD001

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective. Disease must be measurable or evaluable by RECIST criteria.
  • Patients must not have had radiation therapy, hormonal therapy, biologic therapy or chemotherapy for cancer within the 28 days prior to study day 1. Patients must not have had major surgery within the 28 days prior to study day 1 or minor surgical procedures within the 7 days prior to study day 1.
  • Age >18 years.
  • Karnofsky performance status > 70%.
  • Life expectancy of at least 3 months.
  • Patients must have normal organ and marrow function as defined below:

    **Absolute neutrophil count greater or equal to 1,500/μl; Platelets greater or equal to 100,000/μl; Total bilirubin, less or equal to 1.5 X upper limit of normal (ULN)AST(SGOT)/ALT(SGPT)less or equal to 2.5 X ULN less or equal to 5 X ULN if known hepatic metastases; Creatinine clearance greater or equal to 50 mL/min/m2 for patients with creatinine levels (by Cockroft-Gault equation or 24 hour urine; Hemoglobin > 9 g/dL; Magnesium > 1.2 mg/dL; Calcium (corrected for albumin)> 8.7 mg/dL

  • The effect of the investigational drugs on the developing human fetus is not known, but these drugs are likely to be embryo- and feto- toxic. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner are participating in this study, she should inform her treating physician and study PI immediately. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study.
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • Patients who have had radiation therapy, hormonal therapy, biologic therapy, or chemotherapy for cancer within the 28 days prior to day 1 of the study.
  • Patients who have received any other investigational agents within the 28 days prior to day 1 of the study.
  • Patients with known CNS metastases or centrally-located non-small cell lung cancer.
  • Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or diastolic blood pressure > 100 mmHg)
  • Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
  • Symptomatic peripheral vascular disease
  • Evidence of bleeding diathesis or coagulopathy. Patients on full dose anticoagulation are excluded from this trial.
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment (56 days for hepatectomy, thoracotomy, neurosurgery) or anticipation of need for major surgical procedure during the course of the study
  • Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
  • Serious, non-healing wound, ulcer, or bone fracture
  • Proteinuria at screening as demonstrated by Urine protein:creatinine (UPC) ratio greater than 1.0
  • Any prior history of hypertensive crisis or hypertensive encephalopathy
  • New York Heart Association (NYHA) Grade II or greater congestive heart failure
  • History of myocardial infarction or unstable angina within 6 months prior to study enrollment
  • History of stroke or transient ischemic attack within 6 months prior to study enrollment
  • History of intolerance or hypersensitivity to prior treatment with bevacizumab, RAD001, or panitumumab. Prior treatment with these agents is otherwise permitted.
  • Chronic treatment with systemic steroids or another immunosuppressive agent, though steroids may be used on an as-needed basis - ie - for treatment of nausea. Treatment with megace is permitted for treatment of anorexia.
  • Other concurrent severe and/or uncontrolled medical disease which could compromise safety of treatment (i.e., severely impaired lung function, uncontrolled diabetes, uncontrolled hypertension, severe infection, severe malnutrition, ventricular arrhythmias, active ischemic heart disease, chronic liver or renal disease, active upper GI tract ulceration)
  • A known history of HIV seropositivity, hepatitis C virus, acute or chronic active hepatitis B infection.
  • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter drug absorption (e.g., inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or significant small bowel resection)
  • Patients with an active, bleeding diathesis or on oral anti-vitamin K medication (except low dose coumarin)
  • Patients unwilling to or unable to comply with the protocol
  • Medical need for the continued administration of any of the following drugs which affect CYP3A. (see Appendix A ifor a list of common medications).
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit safety or compliance with study requirements or may interfere with the interpretation of the results.
  • History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or any evidence of interstitial lung disease on baseline chest CT scan
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00586443

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Herbert Hurwitz, MD
Novartis
Genentech
Amgen
Investigators
Principal Investigator: Herbert I Hurwitz, MD Duke University
  More Information

No publications provided

Responsible Party: Herbert Hurwitz, MD, Associate Professor of Medicine, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT00586443     History of Changes
Other Study ID Numbers: Pro00001082
Study First Received: December 21, 2007
Last Updated: April 8, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Duke University:
solid tumors
avastin
Phase I
Phase 1
combination therapy
bevacizumab
RAD001
everolimus
pantitumumab

Additional relevant MeSH terms:
Neoplasms
Everolimus
Sirolimus
Antibodies, Monoclonal
Bevacizumab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on April 17, 2014